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Role of the p.E66Q variant of GLA in the progression of chronic kidney disease.
[fabry disease]
The
p
.
E
66
Q
variant
of
the
α-galactosidase
A
gene
(
GLA
)
is
frequently
found
during
screening
for
Fabry
disease
in
dialysis
patients
in
Japan
.
However
,
recent
reports
suggest
that
the
p
.
E
66
Q
variant
is
not
a
disease-causing
mutation
but
is
a
risk
factor
for
cerebral
small
-vessel
occlusion
.
To
evaluate
the
role
of
the
p
.
E
66
Q
in
the
progression
of
renal
diseases
,
we
performed
a
genetic
association
study
in
patients
with
chronic
kidney
disease
(
CKD
)
.
In
this
study
,
we
enrolled
1651
chronic
hemodialysis
and
941
non-dialysis
patients
who
attended
medical
institutions
in
the
Niigata
Prefecture
,
Japan
.
The
frequency
of
the
p
.
E
66
Q
allele
was
compared
between
hemodialysis
and
non-dialysis
patients
,
with
data
from
a
previously
published
study
of
Japanese
male
newborns
.
In
addition
,
we
compared
estimated
glomerular
filtration
rates
(
eGFR
)
in
the
presence
or
absence
of
the
p
.
E
66
Q
variant
in
non-dialysis
patients
.
Of
the
2233
alleles
in
hemodialysis
and
1447
alleles
in
non-dialysis
patients
,
21
and
nine
harbored
p
.
E
66
Q
,
respectively
.
However
,
p
.
E
66
Q
allele
frequencies
did
not
differ
between
the
two
patient
groups
(
0
.
90
versus
0
.
62
Â
%
,
P
Â
=
Â
0
.
35
)
,
and
no
significant
difference
in
p
.
E
66
Q
allele
frequency
was
observed
between
male
hemodialysis
patients
and
the
general
Japanese
population
(
0
.
52
versus
0
.
63
Â
%
,
P
Â
=
Â
0
.
67
)
.
Moreover
,
eGFR
did
not
significantly
differ
between
non-dialysis
patients
with
the
p
.
E
66
Q
variant
and
patients
with
the
wild-
type
allele
(
65
.
5
Â
±
Â
10
.
7
versus
62
.
7
Â
±
Â
16
.
6
Â
mL
/
min
/
1
.
73
Â
m
(
2
)
,
P
Â
=
Â
0
.
69
)
.
This
study
indicated
that
the
p
.
E
66
Q
variant
of
GLA
does
not
affect
the
progression
of
CKD
.
Diseases
Validation
Diseases presenting
"type allele"
symptom
cowden syndrome
erythropoietic protoporphyria
fabry disease
junctional epidermolysis bullosa
severe combined immunodeficiency
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